Term
| what do intercalating agents target? |
|
Definition
| DNA replication and transcription |
|
|
Term
| what do antimetabolites target in cancer cells? |
|
Definition
|
|
Term
| what do spindle poisons target? |
|
Definition
|
|
Term
| what is the mechanism of vinblastine and vincristine? |
|
Definition
| bind to tubulin and prevent polymerization into microtubules - inability to segreagate chromosomes during mitosis leads to cell death |
|
|
Term
| what is the side effect of vincristine? |
|
Definition
|
|
Term
| what is the side effect vinblastine? |
|
Definition
|
|
Term
| How do cells develop resistance to vinblastine and vincristine? |
|
Definition
1)mutations in tubulin
2)P-glycoprotein membrane efflux pump |
|
|
Term
| what is vinblastine used to treat? |
|
Definition
testicular cancer
lymphoma |
|
|
Term
| what is vancristine used to treat? |
|
Definition
childhood leukemia
Hodgkin's disease |
|
|
Term
|
Definition
| depolymerization of microtubules |
|
|
Term
| what two drugs are taxanes? |
|
Definition
|
|
Term
| what is the mechanism of paclitaxel and docetaxel? |
|
Definition
| bind beta subunit of tubulin and atnagonize it disassembly, resulting in bundles of microtubules and aberrant microtubule structures in treated cells |
|
|
Term
| what are paclitaxel and docetaxel used to treat? |
|
Definition
advanced breast/ovarian carcinoma
non-small cell lung carcinoma
Kaposi sarcoma
head/neck cancer |
|
|
Term
| How are paclitaxel and docetaxel excreted? |
|
Definition
|
|
Term
| what is responsible for metabolzing palitaxel and docetaxel? |
|
Definition
|
|
Term
| what are the side effects of paclitaxel and docetaxel? |
|
Definition
hypersensitivity reactions
docetaxel - fluid retention with edema and weight gain |
|
|
Term
| what is responsible for resistance to palitaxel and docetaxel? |
|
Definition
1)increased expression of efflux pumps (P-glycoprotein and mdr-1 gene)
2) beta tubulin mutations |
|
|
Term
|
Definition
| cause DNA-alkylation leading cross linking of DNA which blocks the cell cycle |
|
|
Term
| what two drugs are triazenes? |
|
Definition
decarbazine- methylating agent
temozolomide - prodrug of decarbazine |
|
|
Term
| How is decarbazine administered? |
|
Definition
|
|
Term
| How is temozolomide administered? |
|
Definition
|
|
Term
| what results in resistance to dacarbazine? |
|
Definition
| repair of methylated guanine bases in DNA by an alkyltransferase |
|
|
Term
| what are the side effects of dacarbazine and temozolomide? |
|
Definition
| nausea, vomiting, **myelosuppression, flu-like symptoms, fever, myalgia |
|
|
Term
| what is temozolomide specifically used to treat? |
|
Definition
| brain mets and brain tumor *** VERY important bc few drugs can cross BBB |
|
|
Term
| what is dacarbazine used to treat? |
|
Definition
| advanced malignant melanoma |
|
|
Term
| antitumor antibiotics are a group of antimicrobial compounds produced by __________ |
|
Definition
|
|
Term
| what is the mechanism of dactinomycin? |
|
Definition
| binds with double helical DNA and causes single-strand breaks (via free radicals or topoisomerase II) |
|
|
Term
| how is dactinomycin administered? |
|
Definition
|
|
Term
| what is responsible for resistance to dactinomycin? |
|
Definition
|
|
Term
| can dactinomycin penetrate the BBB? |
|
Definition
|
|
Term
| what is dactinomycin used to treat? |
|
Definition
Wilm's Tumor
rhabdomyosarcoma
Ewing's sarcoma |
|
|
Term
| what is the mechanism of doxorubicin? |
|
Definition
DNA intercalation
DNA-strand breaks by free radical
inhibition of topoisomerase preventing the re-sealing of DNA |
|
|
Term
| how is doxorubicin administered? |
|
Definition
|
|
Term
| how is doxorubicin elminated? |
|
Definition
|
|
Term
| what is the major side effect of doxorubicin? |
|
Definition
| *cardiomyopathy - unresponsive to digitalis |
|
|
Term
| what is doxorubicin used to treat? |
|
Definition
breast cancer
small cell lung cancer
sarcoma |
|
|
Term
| what is responsible for resistance to doxorubicin? |
|
Definition
1)increased efflux via P-glycoprotein
2)increased glutione peroxidase activity
3)decreased activity of topoisomerase II |
|
|
Term
| what is the mechanism of bleomycin? |
|
Definition
| causes oxidative damage resulting in single and double-strand breaks |
|
|
Term
| how is bleomycin administered? |
|
Definition
|
|
Term
| how is bleomycin excreted? |
|
Definition
|
|
Term
| how does mitomycin affect the structure of nucleic acids? |
|
Definition
|
|
Term
| what are the side effects for bleomycin? |
|
Definition
little myelosuppression - good in combo with other cytotoxic drugs
cutaneous toxicity - hyperpigmentation/keratosis
pulmonary toxicity
(cutaneous and pulmonary toxicity due to lack of hydrolase break down in those tissues) |
|
|
Term
| when should the dosage of bleomycin be reduced? |
|
Definition
|
|
Term
| what is the mechanism of resistance against bleomycin? |
|
Definition
1)increased hydrolase activity
2)decreased drug uptake
3)DNA repair |
|
|
Term
| what is bleomycin used to treat? |
|
Definition
used in COMBINATION for
1)testicuar cancer
2)ovarian carcinoma
3) head/neck cancer |
|
|
Term
| what are some examples of biological response modifiers? |
|
Definition
|
|
Term
| what are biological response modifiers (AKA immunotherapy, biotherapy) used for? |
|
Definition
1)to stimulate or restore the ability of the immune system to fight infections, etc
2)to lessen certain side effects of cancer treatment |
|
|
Term
| what is bexarotene used to treat? |
|
Definition
| cutaneous T cell lymphoma |
|
|
Term
| what is the mechanism of bexarotene? |
|
Definition
| binds/activates retinoid X receptors causing cells to stop proliferatins and differentiate |
|
|
Term
| how is bexarotene administered? |
|
Definition
|
|
Term
| how is bexarotene metabolized and eliminated? |
|
Definition
in the liver by CYP450 system - CYP3A4
eliminated in bile |
|
|
Term
| what are the side effects of bexarotene? |
|
Definition
| lipid abnormalities, pancreatitis, GI symptoms |
|
|
Term
| prednisone is converted to _______ in the liver |
|
Definition
|
|
Term
| what synthetic anti-inflammatory glucocorticoid is derived from cortisone? |
|
Definition
|
|
Term
| prednisone is a very powerful ________ |
|
Definition
|
|
Term
| why is prednisone a good cytotosic agent for acute leukemia and malignant lymphoma? |
|
Definition
| because of its lymphocytic effects and its ability to suppress mitosis in lymphocytes |
|
|
Term
| what is prednisone used to treat? |
|
Definition
acute leukemia in kida
malignant lymphoma in kids/adults |
|
|
Term
| what is used for the hormonal treatment of breast cancer? |
|
Definition
| tamoxifen - antiestrogen agent |
|
|
Term
| tamoxifen belongs to what family of compounds? |
|
Definition
| antiestrogens AKA selective estrogen receptor modulators (SERMs) |
|
|
Term
| what can be used for breast cancer prevention in high risk women? |
|
Definition
|
|
Term
| how is tamoxifen administered? |
|
Definition
orally
can be given alone or in combo with other chemo drugs |
|
|
Term
| what are the side effects of tamoxifen? |
|
Definition
| mild nausea, hot flashes, vomiting, weight gain, *bone pain , hair thinning |
|
|
Term
| what drugs can interfere with tamoxifen? |
|
Definition
warfarin
oral contraceptives |
|
|
Term
| what is responsible fore nearly 50 percent of cancers being completely resistant to chemo or only repsonding transiently? |
|
Definition
| MDR= multidrug resistance |
|
|
Term
| what are the mechanisms of drug resistance? |
|
Definition
increased efflux by P-glycoprotein
enzymatic deactivation
altered binding sites
alternate metabolic pathways
decreased permeability |
|
|
Term
|
Definition
ATP dependent membrane transporter and
product of the MDR-1 gene
*responsible for mulitdrug resistance |
|
|
Term
| what do verapamil and cyclosporin A do? |
|
Definition
| inhibit P-glycoprotein so can increase the activity of cytotoxic drugs by increasing their level in the cells |
|
|
Term
| Name 2 alkaloids (microtubule inhibitors): |
|
Definition
1)Vincristine
2)Vinblastine |
|
|
Term
| These 3 drugs have been used to eliminate hypersensitivity reactions to Paclitaxel/Docetaxel |
|
Definition
1)dexamethasone
2)diphenhydramine
3)histamine H2-receptor antagonist |
|
|
Term
| For ___________ clearance is saturable and decreases for increasing dose or dose rate. |
|
Definition
|
|
Term
| decarbazine (DTIC) acts as a _____________. |
|
Definition
|
|
Term
| Temozolomide acts as a ______________. |
|
Definition
| prodrug to dacarbazine (DTIC) |
|
|
Term
| Bleomycin is degraded by what? |
|
Definition
| a specific hydrolase found in many normal tissues (hydrolase activity low in lungs and skin) |
|
|
